P1149: COMPARISON OF THE EFFICACY OF EPCORITAMAB VERSUS CHIMERIC ANTIGEN RECEPTOR THERAPIES, POLATUZUMAB-BASED REGIMENS, AND TAFASITAMAB-BASED REGIMENS
Authors: Allison Rosenthal, Monika Jun, Javier Munoz, Tongsheng Wang, Alex Mutebi, Anthony Wang, Shibing Yang, Kojo Osei-Bonsu, Brian Elliott, Anupama Kalsekar, Fernando Rivas Navarro, Andrew Ip
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Newly approved treatments for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and large B-cell lymphoma (LBCL) include chimeric antigen receptor T-cell (CAR T) therapy, polatuzumab vedotin plus bendamustine and rituximab (pola-BR) and tafasitamab plus lenalidomide (tafa-len). The effectiveness of pola-BR and tafa-len in clinical practice has been evaluated in recent real-world studies (Hamadani et al, ASH 2022; Qualls et al, ASH 2022). Epcoritamab, an off-the-shelf subcutaneous CD3xCD20 T-cell–engaging, bispecific antibody that redirects CD3+ T cells to eliminate malignant CD20+ B cells, has demonstrated deep and durable responses with manageable safety across R/R LBCL patient populations, including those with difficult-to-treat LBCL. In the absence of head-to-head trials, there is a need to assess the comparative efficacy of these therapies. Aims: To compare the efficacy of epcoritamab vs CAR T, pola-based regimens, and tafa-based regimens (including variations of pola-BR and tafa-len) in R/R DLBCL and LBCL. Methods: This study compared individual patient data from the EPCORE™ NHL-1 trial (NCT03625037; Jan 2022 cutoff) and multiple US academic and community clinical practices in the COTA electronic health records database (2010–2022), including adult patients with R/R DLBCL and LBCL treated with CAR T, pola-based, and tafa-based regimens with ≥2 prior lines of therapy (LOTs). Inverse probability of treatment weighting was used to create balanced cohorts on key demographic and clinical characteristics. Outcomes were compared across balanced cohorts: patients treated with epcoritamab vs those treated with other novel therapies (ie, CAR T-naive LBCL patients in EPCORE NHL-1 vs CAR T patients, and all DLBCL patients from EPCORE NHL-1 vs patients treated with pola-based and tafa-based regimens in the COTA database). Overall response rate (ORR) and complete response (CR) rate were compared using weighted logistic models; progression-free survival (PFS) and overall survival (OS) were compared using weighted Cox proportional-hazard models. Results: A total of 96 CAR T-naive LBCL patients were included in the epcoritamab cohort vs 55 in the CAR T cohort (axicabtagene ciloleucel, 60%; tisagenlecleucel, 14.6%), and 139 DLBCL patients in the epcoritamab cohort vs 37 receiving pola-based regimen and 20 receiving tafa-based regimen. Cohorts were balanced on several factors including but not limited to prior CAR T exposure (in epcoritamab vs pola-based and tafa-based regimens), number of prior LOTs, and refractoriness to last LOT. For epcoritamab vs CAR T, CR rate was 38.9% vs 36.5%. For epcoritamab vs pola-based and tafa-based regimens, CR rate was 38.9% vs 10.7% and 11.2%, respectively. Adjusted odds ratio (95% CI) for CR for epcoritamab vs CAR T was 1.14 (0.79, 1.64; P=0.472); for epcoritamab vs pola-based regimens was 3.60 (2.04, 6.37; P<0.0001); and for epcoritamab vs tafa-based regimens was 3.48 (2.01, 6.01; P<0.0001). Adjusted hazard ratio (95% CI) for OS for epcoritamab vs CAR T was 1.08 (0.70, 1.69; P=0.724); for epcoritamab vs pola-based regimens was 0.44 (0.32, 0.62; P<0.0001); and for epcoritamab vs tafa-based regimens was 0.53 (0.38, 0.75; P=0.0003). Other clinical outcomes are summarized in the Table. Summary/Conclusion: Epcoritamab provides significantly better efficacy vs pola-based and tafa-based regimens, with no significant difference vs CAR T, in patients with R/R DLBCL and LBCL who received ≥2 prior LOTs. These findings are subject to limitations consistent with comparative analyses conducted outside of a randomized clinical trial.Keywords: Real world data, Survival, Bispecific, Clinical outcome